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Background  The biological behavior and clinical outcome of esophageal squamous cell carcinoma (ESCC) are difficult to predict.    Methodology/Principal Findings  We investigate the prognostic impact of vascular invasion to establish a risk stratification model to predict recurrence and overall survival. We retrospectively evaluated the vascular invasion of 433 patients with ESCC treated with surgery between 2000 and 2007 at a single academic center. Those patients were assigned to a testing cohort and a validation cohort by random number generated in computer. The presence of vascular invasion was observed in 113 of 216 (52.3%) and 96 of 217 (44.2%) of ESCC in the training and validation cohorts, respectively. Further correlation analysis demonstrated that vascular invasion in ESCC was significantly correlated with more advanced pN classification and stage in both cohorts ( P <0.05). Additionally, presence of vascular invasion in ESCC patients was associated closely with poor overall and recurrence-free survival as evidenced by univariate and multivariate analysis in both cohorts ( P <0.05). In the subset of ESCC patients without lymph node metastasis, vascular invasion was evaluated as a prognostic predictor as well ( P <0.05). More importantly, the combined prognostic model with pN classification supplemented by vascular invasion can significantly stratify the risk (low, intermediate and high) for overall survival and recurrence-free survival in both cohorts ( P <0.05). The C-index to the combined model showed improved predictive ability when compared to the pN classification (0.785  vs  0.739 and 0.689  vs  0.650 for the training and validation cohorts, respectively;  P <0.05).    Conclusions/Significance  The examination of vascular invasion could be used as an additional effective instrument in identifying those ESCC patients at increased risk of tumor progression. The proposed new prognostic model with the pN classification supplemented by vascular invasion might improve the ability to discriminate ESCC patients’ outcome.

Prognostic Significance of the pN Classification Supplemented by Vascular Invasion for Esophageal Squamous Cell Carcinoma